A Unique Virulence Gene Occupies a Principal Position in Immune Evasion by the Malaria Parasite Plasmodium falciparum

摘要: Mutually exclusive gene expression, whereby only one member of a multi-gene family is selected for activation, used by the malaria parasite Plasmodium falciparum to escape human immune system and perpetuate long-term, chronic infections. A genes called var encodes chief antigenic virulence determinant P. malaria. are transcribed in mutually manner, with switching between active resulting variation. While recent work has shed considerable light on epigenetic basis activation silencing, how controlled remains mystery. In particular, seems not be random, but instead appears coordinated result timely individual leading sequential waves antigenically distinct populations. The molecular this apparent coordination unknown. Here we show that var2csa, an unusual highly conserved gene, occupies unique position within hierarchy. Induction through destabilization specific chromatin using both genetic chemical methods repeatedly led rapid var2csa. Additional experiments demonstrated these represent “true” events simply de-silencing var2csa promoter, limited locus chromosome 12. Combined translational repression transcripts, frequent “default” detection untranslated transcripts non-pregnant individuals, data suggest could play central role coordinating switching, fulfilling prediction made mathematical models derived from population patterns. These studies provide first insights into mechanisms which as well example pharmacological agent can disrupt variation falciparum.